Pediatric Pulmonology 34:189-195 (2002)

Series of Laryngomalacia, Tracheomalacia, and Bronchomalacia Disorders and Their Associations With Other Conditions in Children

I.B. Masters, MBBS, FRACP,1* A.B. Chang, PhD, FRACP,2 L. Patterson, MBBS, FANZCAC,1 С Wainwright, MD, FRACP,1 H. Buntain, MBBS,1 B.W. Dean, MSC,1 and P.W. Francis, MD, FRACP1

Summary. Laryngomalacia, bronchomalacia, and tracheomalacia are commonly seen in pediatric respiratory medicine, yet their patterns and associations with other conditions are not well-understood. We prospectively video-recorded bronchoscopic data and clinical information from referred patients over a 10-year period and defined aspects of interrelationships and associations. Two hundred and ninety-nine cases of malacia disorders (34%) were observed in 885 bronchoscopic procedures. Cough, wheeze, stridor, and radiological changes were the most common symptoms and signs. The lesions were most often found in males (2:1) and on the left side (1.6:1). Concomitant malacia lesions ranged from 24%forlaryngotracheobronchomalaciato 47% for tracheobronchomalacia. The lesions were found in association with other disorders such as congenital heart disorders (13.7%), tracheo-esophageal fistula (9.6%), and various syndromes (8%). Even though the understanding of these disorders is in its infancy, pediatricians should maintain a level of awareness for malacia lesions and consider the possibility of multiple lesions being present, even when one symptom predominates or occurs alone. Pediatr Pulmonol Pediatr Pulmonol. 2002; 34:189-195. © 2002 wiiey-Liss. inc.

Key words: laryngomalacia; tracheomalacia; bronchomalacia; malacia disorders; syndromes.

INTRODUCTION The aim of this report is to describe an extensive experience of various forms of laryngomalacia, tracheo­ Tracheomalacia, bronchomalacia, and laryngomalacia malacia, and bronchomalacia and explore some of the disorders are commonly seen in tertiary pediatric respira­ interrelationships that exist between these conditions with tory practice. These disorders of the large airways are respect to their anatomical sites and associations, associated with cough, wheeze, and stridor, covering most of the common respiratory symptoms seen in children. The importance of diagnosing tracheomalacia, broncho­ METHODS malacia, and laryngomalacia ranges from life-threatening A detailed review of the prospectively recorded cli­ disease requiring major diagnostic and surgical interven­ nical features and videotaped bronchoscopic lesions of tions to parental reassurance and withdrawal of drugs the airways from children referred to the authors over a 7 often used to treat these disorders unnecessarily.' ~ In our 10-year period was undertaken. The children were collective experience, many children are only referred for referred to the Royal Children's Hospital and Mater assessment after repeated failures of trials of asthma drug therapies and antibiotics. Department of Respiratory Medicine. Royal Children's Hospital, Herston. However, with the symptoms involved often over­ Brisbane. Queensland, Australia. lapping other respiratory disorders, it is not surprising that the management of these disorders could be viewed as "Flinders University Northern Territory Clinical School, /Mice Springs suboptimal. In addition, the prevalence of these disorders Hospital, Alice Springs, Australia. is not known, and just what relationships exist between "Correspondence to: Dr. I.B. Masters. MBBS, FRACP, Department of these disorders and vascular and cardiovascular disor­ Respiratory Medicine, Royal Children's Hospital. Hcrston. Brisbane 4029. ders, immunological disorders, recurrent bronchitis, bron­ Queensland. Australia. E-mail: [email protected] chiolitis, asthma, chronic suppurative lung disease and pneumonia are also not known, making decisions of Received 27 November 200 I; Accepted 23 May 2002. management even more difficult in terms of diagnostic DOI l0.U)02/ppuU0!5o precision, drug therapies, and long-term prognostication, Published online in Wiley InterScience Avww.intcrscience.wilev.com)

© 2002 Wiley-Liss, Inc. 190 Masters et al. Children's Hospital, Brisbane, from throughout the state the bronchoscope or applied positive airway pressures. of Queensland, Australia, where the total population is The usual appearance of malacia in the left main stem approximately 3 million, of whom 500,000 are children. was that of an "inverted teardrop," with partial or These referral centers handle almost all complex pedi­ complete apposition of the mucosal superior and inferior atric respiratory medicine for the state. surfaces producing a slit-like opening (Fig. 9a,b). Lobar Children with the endoscopic diagnosis of laryngoma- or segmental lesions usually had slit-like or "lunar lacia, bronchomalacia, or tracheomalacia were selected crescent appearances" (Fig. 10a,b). from all bronchoscopic procedures performed. The endoscopic diagnostic features are outlined below, Materials and Bronchoscopic Procedure and examples are given in Figures 1-10. For the purposes of this report, we introduce the term "malacia disorders" All diagnostic information was obtained during flexible to cover the lesions as a group. bronchoscopic procedures performed during spontaneous breathing under gaseous general anesthesia. The anes­ Definition 1 thetic agents used were halothane and or sevoflurane. The vocal cords and trachea were sprayed with lignocaine Laryngomalacia is a long, curved epiglottis, short ary- from a Cass needle or direct spray. Generally, the children epiglottic folds (false cords), prominent and or bulky breathed spontaneously throughout the procedure, and arytenoids and degrees of prolapse of the arytenoids, and positive end expiratory pressure was not usually applied changes in epiglottic appearance and position seen during except during periods of assessment of malacia. The inspiration and returning to the original position during bronchoscope was passed into the airway through a port expiration. in the connector to the facemask. The same four anesthetists were involved in all procedures. All cases Definition 2 were videotaped for later perusal. Anatomical sites and Tracheomalacia is a membranosa deformity in the type of lesion were detailed in each case. All bron­ trachea, maintained during spontaneous respiration but choscopic procedures were performed when the children which could be altered by the passage of the broncho­ were clinically well or stable. A Pentax FB10X 3.5 mm scope or positive airway pressure changes. The descrip­ or Olympus BF 3C40 3.6 mm bronchoscope was used in tive appearances accepted as tracheomalacia are as each case. follows: triangular (Fig. 1), oval/flattening (Fig. 2a-c), localized extrathoracic raised and dynamically bulging Statistics pars membranosa (tracheal dyskinesia) (Fig. 3a,b), and an "Eifel Tower" appearance (Fig. 4a,b). All data were expressed as simple percentages, medi­ Pericarinal tracheobronchomalacia was defined as a ans, and ranges. flattening in the anterior/posterior plane of the trachea, extending into the left and right main-stem bronchi RESULTS (Figs. 5a,b, 6a-c). Tracheomalacia associated with tracheo-esophageal fistula is usually seen as a combina­ Two hundred and ninety-nine cases of laryngomalacia, tion of a dynamically bulging pars membranosa and tracheomalacia, bronchomalacia, and/or combinations of anterior flattening or triangular appearances (Figs. 7a- the three were defined from a total of 885 bronchoscopies d, 8a-c). performed over a 10-year period. This represents 34% of the procedures being defined a "malacia disorder." Definition 3 Malacia disorders were defined in 205 males and 94 females, i.e., a male to female ratio of 2:1. In recognized Bronchomalacia is an appearance of deformity in the syndromes and related disorders, the male predominance large right or left main-stem bronchi, and/or their res­ ranged from 1.6:1 to 8:1. The ratios and associated pective divisions at the lobar or segmental level. The conditions are shown in Tables 1 and 2. appearance of deformity could be altered by a passage of The median age of this cohort was 9 months (range, 1 day to 240 months), with the median age of males being ABBREVIATIONS 9 months, and that of females being 9.6 months. Stridor was reported in 127 (42.5%), and of these, 58 CLE Congenital lobar emphysema CT Cono-truncal (19.4%) reported stridor alone. Wheeze and cough LMS Left main .stem symptomatology was reported in 130 (43.4%) and 212 RMS Right main stem (71%), respectively, while 34 (11.7%) reported all three SYN Syndrome symptoms. These signs were not usually present in very TEF Tracheo-esophageal lislula sick patients, particularly cardiac patients, where unex- Malacia Disorders in Children 191

Fig. 1. Triangular appearance of tracheomalacia. Fig. 4. "Eifel tower" appearance of tracheomalacia (a), and progressive expiratory closure with mucosal surfaces apposed (b).

Fig. 5. Pericarinal right main-stem malacia (a), and progressive closure of right main stem on expiration (b).

Fig. 2. Pericarinal and right and left main-stem malacia. Oval shape (a) and progressive flattening on expiration of pericarinal and right and left main-stem bronchi (b), and complete closure of L main stem bronchi (c).

r

Fig. 3. Bulging pars membranosa: subglottis and proximal trachea: "posterior tracheomalacia." Dynamically bulging pars Fig. 6. Pericarinal and left main-stem malacia (a),and progres­ starting in the subglottis (a), and progressing to less prominent sive closure of left main stem on expiration (b) to complete bulge lower in the trachea (b). closure and mucus extrusion (c). 192 Masters et al.

Fig. 9. Left main-stem bronchomalacia. Left main-stem "inverted teardrop" malacia with (a) and without (b) retained secretions.

Of the 59 children diagnosed with laryngomalacia, 14 (24%) had combined lesions, i.e., laryngotracheobronch- omalacia. Eighty children (26.7%) had tracheomalacia alone, 103 (34.4%) had bronchomalacia alone, and 146 (48%) had some combination of tracheobronchomalacia. There was a male predominance for all of these lesions (Tables 1 and 2). Fig. 7. Tracheo-esophageal fistula malacia. Progressive closure Congenital cardiac disorders and/or cardiovascular with pars bulging forwards (a) and flattened anterior cartilage anomalies were present in 41 (13.7%) patients, of whom (b), proximal to fistula site and progressing from right-to-left triangle (c) to left-to-right triangle appearance (d) lower in the 11 had a vascular ring anomaly, including 3 with a double trachea. aortic arch and 2 with a pulmonary artery sling. Of the 3 patients with a double aortic arch, one had a surgical plained oxygen requirements and radiographic signs were division of the ring because of respiratory failure in the the predominant reason for referral. neonatal period. This produced a marked improvement in One hundred and twelve (37%) had radiographic function, but the appearance changed little over the first abnormalities in the form of parenchymal abnormalities 12 months of life. The two cases of pulmonary artery consistent with any of the following changes of collapse, sling were left unoperated; the associated appearance consolidation, and radio-lucency. of saber-shaped tracheal stenosis and RMS malacia remained unchanged but functionally less important over time. Cono-truncal cardiac disorders were present in 19 cases, with the malacia appearance being universally found in the trachea and/or the left main-stem bronchus. Most had had surgery at the point of assessment, but such lesions were also present in those in whom an operation had not been performed. Tracheomalacia was associated with the primary diagnosis of tracheo-esophageal fistula (TEF) in 29 pa­ tients (9.7%), and congenital lobar emphysema (CLE)

Fig. 8. Tracheo-esophageal fistula malacia with residual pit visible (a), triangular appearance, and an associated anterior Fig. 10. Left upper lobe lobar and segmental bronchomalacia. granuloma (b, c). Left upper lobe malacia (a) and segmental malacia (b). Malacia Disorders in Children 193

TABLE 1 — Age and Gender Distribution of the "Malacia Disorders"

Lm Lm** T Т** В LTB (n = 88) (n = 59) (n= 163) (n = 80) (n=143) (n=14)

Male 57 35 118 55 103 9 Female 31 24 45 25 43 5 M:F 1.54:1 1.45:1 2.6:1 2.2:1 2.4:1 1.8:1 Median age 4Mths 4Mths 15 Mths 15 Mths 9.6 Mths 5 Mths

Lm, laryngi jmalacia in combination; Lm**, laryngomalacia alone; T, tracheomalacia; T*'! :, tracheoma- lacia alone; B, bronchomalacia; LTB, laryn gotracheobronchomalacia; Mths, months.

was found in 9 patients. In the former group with TEF, 6 did the mucosal appearances and associated presence of required aortopexy/tracheopexy because of severe airway mucus. obstruction requiring mechanical ventilation. All pro­ Bronchomalacia was predominantly seen on the left cedures were carried out with bronchoscopic guidance, all side, with 107 (35.7%) left-sided lesions and 66 (22%) patients were extubated successfully, and none required right-sided lesions, the ratio of left:right lesions being further ventilation. The endoscopic appearances were 1.6:1. The malacia was most commonly seen in the left markedly changed at the end of the procedure, with either main-stem (LMS) bronchus (73 cases), followed by the a near-normal appearance or a peaked triangular appear­ left upper lobe bronchus, right middle lobe bronchus, ance sustained across the respiratory cycle. In this latter and right main-stem (RMS) bronchus, with 37, 33, and group of children, the bronchomalacia was at the lobar 31 cases, respectively. Males again predominated, ac­ site of the CLE. There was a male predominance for both counting for 74 (71.8%) of the left-sided lesions and 52 of these disorders (Table 2). (78.7%) of the right-sided lesions. Twenty-four children (8%) had defined syndromes, associations, and/or chromosomal abnormalities including DISCUSSION Down's syndrome, cri du chat syndrome, Rubinstein- Taybi syndrome, Ehlers-Danlos syndrome, Smith's syn­ This is the largest series of large airway lesions drome, Opitz syndrome, Goldenhaar syndrome, Costello's diagnosed by flexible bronchoscopy in children reported syndrome, neurofibromatosis syndrome, Allagille's syn­ to date. We showed that malacia changes are common in drome, Hunter's syndrome, VATER association, CHARGE children referred for persistent respiratory symptoms and association, and arthrogryposis. signs; that combined or multiple lesions commonly over­ Laryngomalacia cases exhibited a variety of functional lap the upper and lower airway compartments either appearances, with varying degrees of prolapse of the serially or concomitantly; and that left-sided lesions are arytenoids and supraglottic rima structures generally. The more common than right-sided bronchomalacia lesions. mucosal appearance in terms of color and apparent These data also suggest that there is a predilection for bulkiness of the arytenoids varied, as did the extent of males to have all forms of malacia disorders. Males are airway closure, with some cases actually displaying com­ thought to have more respiratory disorders early in life plete luminal closure with inspiration. than females, but what the relative risks of such dif­ Tracheomalacia was usually located in the middle and ferences are is not known. Therefore, it is possible that lower thirds of the trachea, but 4 cases were localized to the male predominance in this study merely reflects these the upper airway, where localized sections of the pars differences. However, as there was no separation of age membranosa protruded into the lumen and bulged further ranges between males and females, it is likely that this forwards dynamically with inspiration. The degree of gender effect is real. airway closure associated with these lesions varied, as What role these lesions have in the development of symptoms such as wheeze may be readily accepted in the TABLE 2—Gender Distribution of Malacia Disorders cases of main-stem lesions, but in segmental lesions it Associated With Various Disorders appears to be beyond simple mechanical arguments, unless there is significant peripheral gas-trapping asso­ TEF CT CLE SYN ciated. Nevertheless, persistent respiratory symptoms in n 29 19 9 23 association with lobar and/or segmental airway lesions Male IS 13 8 17 have been well-described.8- ' Exactly why this occurs Female 11 6 1 6 is unknown, but the possibility of a subtle and genera­ Ratio M:F 1.6:1 2:1 8:1 2.8:1 lized etiological process that involves functional abnorm­ TEF, tracheoesophageal fistula; CT, cono-truncal lesions; CLE, alities in the development of the neurovascular and congenital lobar emphysema; SYN, syndrome. airway immunological, smooth muscle, and epithelial 194 Masters et al. cell lines would be biologically possible. It is also well- questions about the importance of gender, laterality in the known that signs or symptoms may persist after surgical development of the lung and airways, and the inter­ interventions, such as tracheopexy/aortopexy on airway relationships of the airway, heart, and blood vessels in the lesions. Follow-up endoscopy often reveals incomplete development of lesions. Similarly, the association of anatomical correction, but concomitant lesions as seen in tracheo-esophageal fistula (TEF) with malacia is inter­ this series should always be considered. esting, but the variable position of the malacia in relation It should also be remembered that the loss of signs, to the fistula and the fact that the malacia may postdate the radiographic changes, and unexplained oxygen require­ TEF surgery again raise concerns about the embryonic ments may be presenting features, particularly in sick origins of these lesions.1-23~2:' Indeed, the sonic hedge­ cardiac patients. hog gene (SHH) has been shown to be important in the The finding of multiple-lesion bronchomalacia in con­ generation of tracheo-esophageal fistulas in mice and junction with tracheomalacia has not been universally humans.26 described, despite relatively large numbers in the pre­ The understanding of the etiological or genetic factors vious series.8'12 It is well-recognized that positioning of that contribute to the development of malacia disorders the bronchoscope, state change, and the application of is in its infancy. Also, there are minimal data on how lignocaine may result in changes in the functional ap­ malacia disorders contribute to respiratory symptoms in pearance of laryngomalacia lesions.13,14 In this study, we children. From the data presented, we suggest that pedi­ carried out the procedures under a general anesthetic, atricians should have an awareness of the possibility of with a local anesthetic agent applied to the glottic and malacia lesions in a child with persistent or recurrent tracheal structures. With respect to airway lesions in­ respiratory symptoms, and we feel the need to be cog­ volving the trachea and bronchi, we do not believe that nizant of the possibility of multiple lesions being present, such appearances could be totally explained by local/ even when one symptom predominates or occurs alone. general anesthetic effects or artificially induced by pres­ In doing so, pediatricians should also be cognizant of the sure dynamics'5 across a shared airway, as the segmental need not to overtreat these disorders with asthma medi­ orifices distal to the malacic orifice are often normal. cations. While developments in gene technologies raise Airway closure during suction is common, and while interesting questions as to the etiology and development suction appears to amplify airway closure in malacic of these lesions, the need for strict definitions utilizing areas, the effect is usually transient. Whatever the effect objective measures should not be underestimated, parti­ of anesthesia, we believe that the bronchoscopic appear­ cularly if further research in this area is contemplated. ances must always be considered in conjunction with the clinical features when defining severity or the need for ACKNOWLEDGMENTS interventional therapy. This series revealed left main-stem lesions to be the The authors acknowledge the anesthetic services of most common. Defining this "inverted teardrop" appear­ Drs. M. Pabari, A. Newton, and G. Maloney. ance is a controversial diagnostic issue.16'17 While this appearance is common at entry into the left main stem, REFERENCES closer inspection often reveals the appearance to be due 1. Lynch JI. Bronchomalacia in children. Considerations governing to the curvature of the left main stem without any medical vs. surgical treatment. Clin Pediatr(Phila) 1970;9:279-282. apparent real reduction in cross-sectional area. While 2. Denneny JC. 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